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Cell Death Dis. 2017 Jun 1;8(6):e2838. doi: 10.1038/cddis.2017.114.

Deficiency of pigment epithelium-derived factor in nasopharyngeal carcinoma cells triggers the epithelial-mesenchymal transition and metastasis.

Zhang T1,2,3, Yin P2, Zhang Z4, Xu B3, Che D1,2, Dai Z2, Dong C2, Jiang P2, Hong H2,5, Yang Z2, Zhou T2, Shao J4, Xu Z2,6, Yang X1,2,7, Gao G1,2,8.

Author information

1
Program of Molecular Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
2
Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
3
Department of Laboratory Medicine, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, China.
4
Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou 510160, China.
5
Department of Clinical Laboratory, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China.
6
Cancer Center, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
7
Guangdong Engineering &Technology Research Center for Gene Manipulation and Biomacromolecular Products (Sun Yat-sen University), Guangzhou 510080, China.
8
China Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China.

Abstract

Distant metastasis is the primary cause of nasopharyngeal carcinoma (NPC) treatment failure while epithelial-mesenchymal transition (EMT) is the critical process of NPC invasion and metastasis. However, tumor-suppressor genes involved in the EMT and metastasis of NPC have not been explored clearly compared with the oncogenes. In the present study, the expression of pigment epithelium-derived factor (PEDF), a potent endogenous antitumor factor, was diminished in human NPC tissues and associated with clinicopathological and EMT features. The knockdown of PEDF induced EMT in lower metastatic NPC cell lines and overexpression of PEDF restored epithelial phenotype in higher metastatic NPC cell lines with typical EMT. The inhibition of PEDF mediated NPC cell spontaneous metastasis in vivo. LRP6/GSK3β/β-catenin signal pathway rather than AKT/GSK3β pathway was involved in the effects of PEDF on EMT. The expression of PEDF was directly downregulated by elevated miR-320c in NPC. In conclusion, our findings indicate for the first time that PEDF functions as tumor-suppressor gene in the occurrence of EMT and metastasis in NPC. PEDF could serve as a promising candidate for NPC diagnosis, prognosis and treatment.

PMID:
28569772
PMCID:
PMC5520876
DOI:
10.1038/cddis.2017.114
[Indexed for MEDLINE]
Free PMC Article

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